Download Metformin associated Atrial Fibrillation - A Case Report

Metformin associated Atrial Fibrillation
- A Case Report
Hemant Boolani, David Shanberg, Vineela Chikkam and Dhanunjaya Lakkireddy
Kansas University Cardiovascular Research Institute, Mid America Cardiology, University of Kansas Hospital
& Medical Center, Kansas City, KS 66195
Introduction
Metformin is an oral antidiabetic drug used for
treatment of Type 2 diabetes mellitus (T2DM).1
It acts by decreasing gluconeogenesis in the liver
and absorption of glucose from the gastrointestinal system, in addition to increasing the peripheral utilization of glucose.2 Metformin is excreted
unchanged through the renal route. Severe side effects are noted in patients with renal and/or hepatic
dysfunction. These may vary from severe lactic acidosis which can be life threatening, to cardiac arrhythmias.3
We present a case of a patient who presented with
recurrent atrial fibrillation with repeated administration of metformin. He developed lactic acidosis
in the absence of renal or hepatic dysfunction and
developed the arrhythmia, which promptly resolved metformin withdrawal.
Presentation
A 68-year-old patient was seen in our clinic for
atrial fibrillation (AF). His past medical history
was pertinent for hypertension, T2DM, anxiety
disorder, coronary heart disease and hyperlip-
idemia. Past surgical history was positive for
coronary artery by-pass graft (CABG). Current
medications include lisinopril, atorvastatin, glimipride, sitagliptin, metoprolol, and warfarin.
At presentation, his BP was 120/74 mmgHg,
Heart Rate 61 beats/min, and respiratory rate
was 14 breaths/min. His physical examination
was unremarkable. An electrocardiogram revealed a normal sinus rhythm (NSR). The patient had a comprehensive metabolic panel which
was essentially within normal limits (Table 1).
On his follow-up visit to his primary physician,
his sitaglipitin was discontinued and metformin
was initiated. After being on it for approximately
seventy two hours, the patient reported irregular
heartbeats and presented to the emergency room.
He was noted to be in atrial fibrillation at the time.
The patient reported a similar episode in the past
when he was on metformin, which resolved when
he discontinued the medication. During this episode, the patient was treated for atrial fibrillation and the metformin was stopped. The patient
converted to NSR upon discontinuation of the
medication after 48 hours. After the rhythm was
normalized, he was rechallenged with metformin.
Corresponding Address : Dhanunjaya Lakkireddy MD, FACC, FHRS, Associate Professor of Medicine, Director, Center for
Excellence in Atrial Fibrillation & Electrophysiology Research, Bloch Heart Rhythm Center – Mid America Cardiology, KU
Cardiovascular Research Institute- University of Kansas Hospital & Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66195.
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Sep-Nov, 2011 | Vol 4 | Issue 3
Journal of Atrial Fibrillation
Case Report
Table 1
Laboratory Values
Labs
Pre Metformin
During Metformin
After stopping metformin
Na mmol/L
138
140
139
K mmol/L
4.1
4
3.9
Cr mg/dL
0.9
1
1
BUN mg/dL
24
30
32
Gluc mg/dL
120
118
124
Chloride mmol/L
105
106
102
CO2 mmol/L
24
19
25
LDH mcmol/L
220
320
184
After approximately 48 hours, he developed AF
(Figure 1). Again, after withdrawal of metformin,
the rhythm reverted to NSR (Figure 2).
spite normal hepatic and renal function and developedlactic acidosis during metformin administration, which might have led to the initiation of AF.
Discussion
Metformin has been used as a first line agent for
treatment of diabetes mellitus along with lifestyle
changes.4 It is not uncommon to see renal or hepatic dysfunction in patients with diabetes, and this
dysfunction may lead to more incidents of lactic
acidosis. Lactic acidosis associated with metformin
has been linked to various side effects, including
cardiac arrhythmias.3, 5 Studies on animal models
have shown that metformin can cause greater dispersion of the QT interval at higher concentrations
This present case illustrates how metformin induced AF each time after repeated challenges to the
patient. On lab data analysis, the renal and hepatic
indices were within normal limits. Interestingly,
the bicarbonate level was noted to be lower when
challenged with metformin, and lactate levels were
higher during the challenge. This suggested the
patient had problems metabolizing metformin deFigure 1: ECG of the patient in atrial fibrillation on metformin
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Sep-Nov, 2011 | Vol 4 | Issue 3
Journal of Atrial Fibrillation
Case Report
Figure 1: ECG of the patient when converted to sinus rhythm after with-holding metformin
and could be responsible for arrhythmogenesis.6
This is the first reported human case of AF related
to metformin use. We hypothesize that lactic acidosis related to metformin use could have potentially
set the AF triggers in motion and have resulted in
substrate changes that perpetuated the arrhythmia.
tensive blood-glucose control with metformin on complications
in overweight patients with type 2 diabetes (UKPDS 34). Lancet
1998; 352: 854-65. [2] Kirpichnikov D, McFarlane SI, Sowers JR.
Metformin: an update. Ann Intern Med 2002; 137: 25-33.
[3] Chang CT, Chen YC, Fang JT, Huang CC. Metformin-associated lactic acidosis: case reports and literature review. J Nephrol
2002; 15: 398-402.
[4] Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR,
Sherwin R, et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of
therapy: update regarding thiazolidinediones: a consensus statement from the American Diabetes Association and the European
Association for the Study of Diabetes. Diabetes Care 2008; 31: 1735.
[5] Heaney D, Majid A, Junor B. Bicarbonate haemodialysis as a
treatment of metformin overdose. Nephrol Dial Transplant 1997;
12: 1046-7.
[6] Costa EC, Goncalves AA, Areas MA, Morgabel RG. Effects of
metformin on QT and QTc interval dispersion of diabetic rats. Arq
Bras Cardiol 2008; 90: 232-8.
Conclusions
Our patient showed recurrence of atrial fibrillation
when re-challenged with the same medication and
resolution on withdrawal of the same medication.
Lactic acidosis is amongst the most rare but significant side effects of metformin and the acidic milieu
as a result of lactic acidosis could make the heart,
particularly the atria more prone to arrhythmias.
References
[1] UK Prospective Diabetes Study (UKPDS) Group. Effect of in-
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